This Head Injury Clinical Research Center Grant at the University of Kentucky is a coordinated multidisciplinary research program which: 1) tests whether insulin-like growth factor-1/Growth Hormone improves neurologic outcome after head injury; 2) investigates the mechanisms of actions of peptide mediators (cytokines) and growth factor in the secondary central and peripheral sequelae of injury. The Grant consists of five projects a and three core facilities. The clinical project tests whether and how intravenous administered IGF- 1/Growth Hormone improves the outcome of severely head injured patients. One project tests the hypothesis that cytokines and tropic factors play an important role in the brain's self-repair process following severe brain injury. The third project tests the hypothesis that the brain's response to injury involves a specific set of gene related protein products which are stimulated by early free radical formation and may be altered by both metabolic products which are stimulated by early free radical formation and may be altered by both metabolic and free radical trapping methods. The fourth project tests the hypothesis that patients with head trauma are predisposed to sepsis-induced lung injury because elevated cytokine levels prime the resident population of pulmonary intravascular macrophages to increase coupling between oxygen radical- dependent bacterial killing and release of mediators which injure the pulmonary vascular bed. The fifth project will test the hypothesis that the liver, the largest reservoir of tissue macrophages in the body, plays an important role in many metabolic abnormalities/complications following brain injury. There is an extraordinarily high degree of interaction among the various investigators. The investigations are directed at defining a wide range of biological and physiological factors which can 1) negatively affect outcome after head injury; and 2) when modulated by growth factors, improve outcome after head injury.